Corrupted Science–BMJ Review Examines Avandia Literature

A systematic review by researchers from the Mayo Clinic assessed bias in 202 published reports, reviews and opinion pieces by 180 authors who wrote about the risk of heart attack and the diabetes drug, Avandia.

The open access report, "Association Between Industry Affiliation and Position on Cardiovascular Risk with Rosiglitazone…" was published in the BMJ (British Medical Journal).

The authors explored possible links between these authors’ financial interests and their opinions. They then had independent reviewers with no conflicts of interest grade each of the 202 articles "as favorable, neutral or unfavorable, based on the authors’ positions on an association between Avandia and heart attacks and on their recommendations for continuing or ending its use. "

Suprise, surprise: Of those who offered favorable views, 87% had potential conflicts with GlaxoSmithKline, the drug’s manufacturer. Among authors who had unfavorable opinions, only 20 percent had received money from Glaxo."  However, the reviewers found that only 53% of authors disclosed their financial interests.

Furthermore, they note, "Given that no formal database exists for reporting conflicts of interest, our findings may very well underestimate the prevalence of conflicts of interest among authors weighing in on rosiglitazone’s safety. We also could not assess the extent to which the observed association reflects ghostwriting in publications related to rosiglitazone."

The BMJ is to be commended for posting a web supplement listing all 202 articles, citing all of the 180 scientists whose papers were studied.

The BMJ authors’ conclusion:

"Disclosure rates for financial conflicts of interest were unexpectedly low, and there was a clear and strong link between the orientation of authors’ expressed views on the rosiglitazone controversy and their financial conflicts of interest with pharmaceutical companies."

The authors note that the findings "underscore the need for further changes in disclosure procedures in order for the scientific record to be trusted."

In interviews with The New York Times, Dr. Rudy Bilous and Dr. Mark W. Stolar, two of the scientists who received payments from Glaxo — and reported favorable findings on Avandia — acknowledged that the financing could create an appearance of bias.

Dr. Bilous, an endocrinologist at James Cook University Hospital in Middlesbrough, England, said: “We can’t have it both ways…”

And Dr Stolar, professor of clinical medicine at Northwestern acknowledged: "There are very few people in whom I don’t detect bias based on where their conflicts lie.”

Vera Hassner Sharav


THE NEW YORK TIMES
April 12, 2010
Study Sees a Slant in Articles on Drug
By NICHOLAS BAKALAR

A new analysis of reviews and articles about the controversial diabetes drug Avandia has found that experts who were paid by its manufacturer have been significantly more likely than others to draw positive conclusions about the drug’s safety and efficacy.

Since 2007, scientists have published hundreds of studies, reviews and opinion articles about Avandia in scientific journals and elsewhere, arriving at a range of conclusions, some sharply opposed to one another.

Avandia, or rosiglitazone, is prescribed, along with diet and exercise, to help control blood glucose levels in people with Type 2 diabetes. In 2007, The New England Journal of Medicine published a review of studies and concluded that its use was associated with a significant increase in the risk for heart attack.

After a Congressional investigation, the Food and Drug Administration imposed a “black box” safety warning on the medicine. In February, The New York Times described confidential F.D.A. reports recommending that Avandia be removed from the market.

To explore possible links between authors’ financial interests and opinions, researchers reviewed 202 articles by 180 authors who wrote about Avandia and the risk of heart attack. Then they had independent reviewers with no conflicts of interest grade each article as favorable, neutral or unfavorable, based on the authors’ positions on an association between Avandia and heart attacks and on their recommendations for continuing or ending its use. The study was published online on March 18 in the journal BMJ.

Often, authors with favorable opinions of the drug were paid both by Avandia’s maker, GlaxoSmithKline, and by its competitors. Of those who offered favorable views, 87 percent had potential conflicts with Glaxo. Among authors who had unfavorable opinions, only 20 percent had received money from Glaxo.

Mary Anne Rhyne, a spokeswoman for Glaxo, said in an e-mail message: “Of the 202 articles, only 10 were original scientific research. Many of the articles reviewed were opinion pieces — editorials, commentaries or letters. It is important to note that the authors’ conclusions do not impugn the validity of the scientific data.”

The BMJ study included a supplement listing all the scientists whose papers were studied. In interviews last week, Dr. Rudy Bilous and Dr. Mark W. Stolar, two of the scientists who received payments from Glaxo — and reported favorable findings on Avandia — acknowledged that the financing could create an appearance of bias.

“We can’t have it both ways,” said Dr. Bilous, an endocrinologist at James Cook University Hospital in Middlesbrough, England. “If people want drugs, the only people in the current environment doing the work and funding the research are the pharmaceutical industry, and their concern is for licensing, not necessarily the science.”

Dr. Stolar, a professor of clinical medicine at Northwestern, had a similar view. “There is no broad enough funding on the national level for significant research,” he said. “The problem is that the interpretation of the findings gets skewed because of that. There are very few people in whom I don’t detect bias based on where their conflicts lie.”

The BMJ review found that 90 of the 202 articles were by people with potential conflicts, but only 69 of them had a statement disclosing the fact. They uncovered the 21 remaining conflicts by searching the Internet and other publications by the same authors.

The study’s authors acknowledged that their work was observational and that they were unable to assign a monetary value to any of the relationships they found.

Dr. Amy T. Wang, the lead author and a resident in internal medicine at the Mayo Clinic, emphasized that the study drew no conclusions about the safety or efficacy of Avandia.

Ms. Rhyne said GlaxoSmithKline “will disclose research payments made to health care professionals and their institutions” beginning in 2011, with the disclosures covering research studies that began on or after Jan. 1, 2010.